Max haedtmann



Patented Oct. 4, 1932 UNITED STATES PATENT OFFIOE WINFRID HENTRIGH ANDltIAX HARDTIVIANN, OF WIESDOR-F-ON-THE-RHINE, GER- MANY, ASSIGNORS TO I.G. FARBENINDUSTRIE AKTIENGESELLSCHAFT, OF FRANK- FORT-ON-THE-MAIN,GERMANY, A CORPORATION OF GERMANY NITRO-HALOGENQUINAZOLINE AND'THEPROCESS OF PRODUCING SAME No Drawing. Application filed November 30,1929, Serial No. 410,870, and in Germany December 3, 1928.

The present invention relates to a process of preparingnitro-halogenquinazolines and to the new products obtainable thereby,more particularly itrelates to compounds of the probable generalformula:

wherein Hal represents a halogen atom, X stands for hydrogen or aradical of the benzene series, and the N0 group is attached to the 6- or7 position, and wherein the benzine nucleus B may be furthersubstituted.

Our new compounds are obtainable by reacting upon anitro-hydroxy-quinazoline of 2 the general formula: I

un e N O2NR I when the evolution of hydrohalic acid ceases.

When working with phosphorus oxychloride as halogenating agent, thereaction can only be effected under superatmospheric pressure. Thestarting nitro-hydroxy-quinazolines are obtainable according to knownprocesses, for example by melting together Intro-anthranilic acid and acompound of the general formula: H N.CO.R, R meaning hydrogen or aryl.

Our new compounds are generally yellow- EXAMPLE 16-m't7'0-4-ohloro-guinazolne ozN-m N 191 parts by weight of6-nitro-L-hydroxy- 'quinazoline (compare Bogert, Journalof the AmericanChemical Society, vol. 34;, page 524, and vol. 41, page 2067) arestirred with 250 parts by weight of phosphorus oxychloride and heatedwith 210 parts by weight of phosphorus pentachloride at 110-130 C. Whenthe evolution of hydrogen chloride ceases the phosphorus oxychloride isdistilled off in the vacuum of the water-jet vacuum pump. At 170 C.asublimation ofthe chloronitro compound begins, thenup to 210 C. thegreater part of the 6-nitro-4-chloroquinazoline distils over with slightdecomposition of the residue. l/Vlien working up larger quantities orless pure materials distillation is ad vantageously avoided (compareExample 2). The 6-nitro4echloroquinazoline crystallizes in the form ofyellow needles, melting at 128 C.; it is very readily soluble in acetoneand ethylaceftate and more difliculty soluble'in benzene, ether and hotligroin. Its odor slightly resembles that of acetamide. The

chlorine in the 4:POSltiOIl is very readily replaceable and even withcold water the reformation of 6-nitro-et-hydroxyquinazoline takes placeafter some time.

EXAMPLE 2 191 parts by weight of 7-nitrol-hydroxy quinazoline(obtainable from l-nitro-Q-aminobenzoic acid andformamideuby heating for6 hours first at 1 10 C. and finally at 170 C.) are stirred with 260parts by weight of phosphorus oXychloride; 208 parts by weight ofphosphorus pentachloride are then added, and the mixture is heated in anoil bath to gentle boiling until the evolution of hydrochloric acidceases. To the reaction mixture 300 100 parts by weight of drychlorobenzene are added and the phosphorus oxychloride is distilled offwhereby over-heating is carefully avoided, until the thermometerindicates the beginning of the distillation of chlorobenzen-e.Thereafter the chlorobenzene and some still adhering phosphoruso'xychloride are distilled off in the vacuum of the water jet vacuumpump to a bath temperature of 110 C. The residue is comminuted andextracted with boiling dry benzene, filtered from the residue andevaporated while carefully excluding access of moisture, until theseparation of crystals begins. The 7 -nitro-4- chloroquinazolinecrystallizes in the form of yellowish needles; it melts at 148 C. It isreadily soluble in acetone and ethyl acetate, more diflicultly solublein cold benzene and fairly readily soluble in hot benzene. By heating toa bath temperature of 200230 C. the 7 -nitro-4l-chloroquinazolinesublimes in the vacuum of the water-jet vacuum pump with partialdecomposition of the residue. lVater re-forms the7-nitro-4c-hydroxyquinazoline.

EXAMPLE 3 6-n itr0-4-chZ0r0-7-methyZ-gwinaeoline I H3o N I r (a)Preparation of 6-nitro-4-hydroXy-7- methylquinazoline: 196 partsbyweight of 5-nitro-2-amin'ol-methylbenzoic acid (nitro homoanthranilicacid) are first heated for 6 hours with 1000 parts by weight offormamide at 140-150" C. The mixture first forms a solution but aftersome time the melt becomes almost solid. As'soonas' the evolution ofwater and ammonia becomes more slow, the reaction is completed byheating the mixture for a further 2 hours at 170 17 5 C. The cooled meltis boiled with water to remove the excess of forma-mide. undissolvedportion is dissolved in the requisite amount of caustic soda solutionand the sodium salt of the 6-nitro-4-hydroxy 7- methylquinazoline isprecipitated as a yellowish crystalline compound which has no distinctcrystal form. By means of hydrochloric acid the free6-nitro-4-hydroXy-7- methylquinazoline is obtained from the salt. Itmelts at 278 (1.; when crystallized from pyridine it forms yellowishgranular crystals.

(6) Preparation of ,6-nitro-et-chloro-7- methylquinazoline: 205 parts byweight of the above substance are stirred with 300 parts by weight ofphosphorus oxychloride. 210 partsby weight of phosphorus pentachlorideare then added, and the mixture is heated at 120-130 C. until theevolution of hydrochloric acid ceases. Thereupon the phosphorusoxychloride is first distilled ofithe vacuum of the water-jet vacuumpump at water bath temperature; after that the temperature is raised toabout 190 C. and the 6-nitro- 1- chloro-7-methylquinazoline distilsover. It melts at 110 0.; it is readily soluble in hot benzene andacetone.

EXAMPLE 4 7-nitr0-4-chloro z-pheng l-guinaeoline (0,) Preparation of 7-nitro-4-hydr0Xy-2- phenylquinazoline: 210 parts by Weight of theethylester of 1-nitro-2-amino-benzoic acid are heated in a closed vesselfor 10 hours at 140-150 C. with a solution of 28 parts byweight ofsodium in 600 parts byweight of absolute alcohol, which contains 1% ofammonia and-120' parts by Weight of benzonitrile. I tered by suction,dissolved in therequisite amount of caustic soda solution, freed fromadhering unchanged benzonitrileby extraction with ether or by passingthrough ater vapor. The7-nitro-4t hydroxy-2-phenylquinazoline obtainedis precipitated by acidifying the solution. After drying it melts at240-250 C. with decomposition (depending on the rapidity of theheating).

(1)), Preparation of 7 -nitro-4-chloro-2- phenylquinazoline: Theconversion of the a-hydroxy compound to the 4=-chloro derivative and theworking up of the reaction mixture are efiected as described in Examiple2. The -nitro-t-chloro-2-phenylquin-- The 7 The precipitate obtainedisifil- I azoline crystallizes from boiling toluene in the form of smallyellow needles. It is very readily decomposed when exposed to moisture.The analysis gave 7 82% of chlorine (calculated 8.04%); 6.68% ofnitrogen, (calculated 6.80%).

In a manner analogous to the preparation of the above describedphenylquinazoline compounds, quinazoline substituted in the phenylresidue may be built up.

We claim:

1. The process which comprises causing a phosphorus halogen compound anda compound of the probable general formula:

(I311 O a any OzN

wherein Y represents hydrogen or a radical of the benzene series, the N0group stands in'one of the positions 6 and 7, and wherein the benzenenucleus It may be further substituted by a-lkyl, to react upon eachother in about equimolecular proportions at a temperature between about80 and 140 C.

2. The process which comprises causing phosphorus pentachloride and acompound of the prob-able general formula:

perature of about 110 to 130 C. and in the -presence of phosphorusoxychloride as a solvent, until the evolution of hydrogen chloride hasceased.

4:. As new products the compounds of the probable general formula:

Hal

wherein Hal represents a halogen atom, the N0 group stands in one of thepositions 6 and 7, X stands for hydrogen or a radical of the benzeneseries, and wherein the benzene nucleus B may be further substituted byalkyl, said compounds being generally yellowish colored crystallinesubstances, soluble in the usual organic solvents.

5. As new products the compounds of the probable general formula:

wherein the N0 group stands in one of the positions 6 and7, X representshydrogen or a radical of the benzene series, and wherein the benzenenucleus B may be further substituted by alkyl, said compounds beinggenerally yellowish colored crystalline substances, soluble in the usualorganic solvents.

6. As new products the compounds of the probable general formula:

om R

wherein the N0 group stands in one of the positions 6 and 7 X stands forhydrogen or phenyl, and wherein the benzene nucleus B may be furthersubstituted by alkyl, said compounds being yellowish colored crystallinesubstances, soluble in the usual organic solvents.

7 As a new product the compound of the probable formula:

being a yellow colored crystalline substance,

melting at 128 0., being very readily soluble in acetone and ethylacetate and more difilcultly soluble in benzene, ether and hot ligroin.

8; As a new product the compound of the probable formula being a yellowcolored crystalline substance, melting at 148 C. andbeing very readilysoluble in acetone and ethyl acetate and more diificultly solubleinbenzene,ether and hot ligroin.

9. As a new produot the compound of the probable formula: 1

. being a yellowish colored substance melting at 110 C. and beingreadily soluble in hot benzene and acetone.

In testlmony whereof, We afix our slgnatures.

WINFRID- HENTRIGH.

' 15 MAX HARDTMANN.

